Freezing the Heart to Save the Life

WHY COLD WORKS

Becker, the director of the Penn Center for Resuscitation Science, seems like a friendlier version of TV’s Gregory House—a detective in a white coat and scrubs. As a medical resident in Chicago in the early 1980s, he found himself attracted to the ER (to the “really, really sick patients,” he says) because he found the task of deducing what was wrong with them more interesting than the treatment.

After spending his early career at Michael Reese Hospital in Chicago, Becker started questioning the published statistics about cardiac arrest. (A heart attack is what happens when blood flow to the heart is restricted; cardiac arrest means the heart has suddenly just stopped. The latter is much rarer.) He had read that 18 percent of patients survive, but, he says, “I knew after working in the emergency department for a while that [that figure] wasn’t anything close to reality.” So in 1989 he analyzed data from hospital and paramedic reports for more than 3,000 local cases. He found that the rates were off by a factor of 10—only 1.8 percent of cardiac-arrest victims in Chicago lived. (The earlier studies were performed in small cities, where patients were typically reached more quickly and were more likely to receive CPR from a bystander.) Three years later, a study in New York City came up with a similar number: 1.4 percent.

But why were people dying even after their hearts had restarted? The question nagged at Becker as he began his assistant professorship at the University of Chicago Hospital in the early 1990s. Scientists believed that when the heart stopped pumping oxygen-rich blood, cells started to die. If that were true, then cells should fare better when the heart starts pumping again. “What we saw was almost the opposite,” he says. Becker watched heart cells under a microscope as he deprived them of oxygen for an hour. Then he gave them oxygen, or “re-perfused” them, for another three hours. Only 4 percent of the cells showed damage initially, but 73 percent showed signs of injury immediately after the oxygen came back. He realized that there was something destructive about the sudden recirculation of oxygen.

Two more years of experiments revealed one of the key mechanisms. Tiny organelles called mitochondria use oxygen to produce energy, and they do so very carefully—add or subtract an electron from an oxygen atom at the wrong time, and it becomes a free radical, an ion powerful enough to damage cell structures and mutate DNA. Cells have systems in place to prevent these dangerous chain reactions, and to maintain other delicate ion balances, but without oxygen those systems break down. When oxygen flow returns, the mitochondria start producing hordes of free radicals; other cellular ion levels also go awry. The injured cells start dying, and in response, the immune system releases chemicals that worsen the effect. The problem is most pronounced in the heart and the brain, which use more oxygen than other organs.